Abstract
N - (benzyloxycarbonyl) - L - aspartyl - L - phenylalanine methyl ester, the precursor of the synthetic sweetener aspartame, was continuously synthesized in an organic solvent with immobilized thermolysin. Ethyl acetate was found to be the most effective organic solvent for the synthesis of this precursor. The plug flow type reactor was found unsuitable, because the immobilized enzyme in it was gradually inactivated even if calcium, the essential stabilizing factor for thermolysin, was added to the substrate. In addition, a severe channeling of the flow occurred in a column. A stirred tank reactor was successfully operated for over 300 hours with a yield of approximately 90 percent and a large space velocity.
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Nakanishi, K., Kamikubo, T. & Matsuno, R. Continuous Synthesis of N-(Benzyloxycarbonyl)-L-Aspartyl-L-Phenylalanine Methyl Ester with Immobilized Thermolysin in an Organic Solvent. Nat Biotechnol 3, 459–464 (1985). https://doi.org/10.1038/nbt0585-459
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DOI: https://doi.org/10.1038/nbt0585-459